Proton therapy
   HOME

TheInfoList



OR:

In medicine, proton therapy, or proton radiotherapy, is a type of particle therapy that uses a beam of
proton A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...
s to irradiate diseased tissue, most often to treat
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. The chief advantage of proton therapy over other types of
external beam radiotherapy External beam radiotherapy (EBRT) is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body. In contrast to brachy ...
is that the dose of protons is deposited over a narrow range of depth; hence in minimal entry, exit, or scattered radiation dose to healthy nearby tissues. When evaluating whether to treat a tumor with photon or proton therapy, physicians may choose proton therapy if it is important to deliver a higher radiation dose to targeted tissues while significantly decreasing radiation to nearby organs at risk. The
American Society for Radiation Oncology ASTRO (the American Society for Radiation Oncology) is a professional association in radiation oncology Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of ...
Model Policy for Proton Beam therapy says proton therapy is considered reasonable if sparing the surrounding normal tissue "cannot be adequately achieved with photon-based radiotherapy" and can benefit the patient. Like photon radiation therapy, proton therapy is often used in conjunction with surgery and/or chemotherapy to most effectively treat cancer.


Description

Proton therapy is a type of external beam radiotherapy that uses
ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
. In proton therapy, medical personnel use a particle accelerator to target a
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
with a beam of protons."Zap! You're Not Dead". ''The Economist'', 8 September 2007. 384 (8545):13–14. These charged particles damage the DNA of cells, ultimately killing them by stopping their reproduction and thus eliminating the tumor. Cancerous cells are particularly vulnerable to attacks on DNA because of their high rate of division and their limited ability to repair DNA damage. Some cancers with specific defects in DNA repair may be more sensitive to proton radiation. Proton therapy lets physicians deliver a highly conformal beam, i.e. delivering radiation that conforms to the shape and depth of the tumor and sparing much of the surrounding, normal tissue. For example, when comparing proton therapy to the most advanced types of photon therapy—intensity-modulated radiotherapy ( IMRT) and volumetric modulated arc therapy (VMAT)—proton therapy can give similar or higher radiation doses to the tumor with a 50%-60% lower total body radiation dose. Protons can focus energy delivery to fit the tumor shape, delivering only low-dose radiation to surrounding tissue. As a result, the patient has fewer side effects. All protons of a given energy have a certain penetration range; very few protons penetrate beyond that distance. Also, the dose delivered to tissue is maximized only over the last few millimeters of the particle's range; this maximum is called the ''spread out
Bragg peak The Bragg peak is a pronounced peak on the Bragg curve which plots the energy loss of ionizing radiation during its travel through matter. For protons, α-rays, and other ion rays, the peak occurs immediately before the particles come to re ...
'', often called the SOBP (see visual). To treat tumors at greater depth, one needs a beam with higher energy, typically given in eV ( electron volts). Accelerators used for proton therapy typically produce protons with energies of 70 to 250 MeV. Adjusting proton energy during the treatment maximizes the cell damage within the tumor. Tissue closer to the surface of the body than the tumor gets less radiation, and thus less damage. Tissues deeper in the body gets very few protons, so the dose becomes immeasurably small. In most treatments, protons of different energies with Bragg peaks at different depths are applied to treat the entire tumor. These Bragg peaks are shown as thin blue lines in the figure in this section. It is important to understand that, while tissues behind (or deeper than) the tumor get almost no radiation, the tissues in front of (shallower than) the tumor get radiation dosage based on the SOBP.


Equipment

Most installed proton therapy systems use isochronous cyclotrons. Cyclotrons are considered simple to operate, reliable and can be made compact, especially with use of
superconducting magnets A superconducting magnet is an electromagnet made from coils of superconducting wire. They must be cooled to cryogenic temperatures during operation. In its superconducting state the wire has no electrical resistance and therefore can conduct much ...
.
Synchrotron A synchrotron is a particular type of cyclic particle accelerator, descended from the cyclotron, in which the accelerating particle beam travels around a fixed closed-loop path. The magnetic field which bends the particle beam into its closed ...
s can also be used, with the advantage of easier production at varying energies. Linear accelerators, as used for photon radiation therapy, are becoming commercially available as limitations of size and cost are resolved. Modern proton systems incorporate high-quality imaging for daily assessment of tumor contours, treatment planning software illustrating 3D dose distributions, and various system configurations, e.g. multiple treatment rooms connected to one accelerator. Partly because of these advances in technology, and partly because of the continually increasing amount of proton clinical data, the number of hospitals offering proton therapy continues to grow. FLASH radiotherapy is a technique under development for photon and proton treatments, using very high dose rates (necessitating large beam currents). If applied clinically, it could shorten treatment time to just one to three 1-second sessions, and further reducing side effects.


History

The first suggestion that energetic protons could be an effective treatment was made by Robert R. Wilson in a paper published in 1946 while he was involved in the design of the Harvard Cyclotron Laboratory (HCL). The first treatments were performed with particle accelerators built for physics research, notably Berkeley Radiation Laboratory in 1954 and at
Uppsala Uppsala (, or all ending in , ; archaically spelled ''Upsala'') is the county seat of Uppsala County and the fourth-largest city in Sweden, after Stockholm, Gothenburg, and Malmö. It had 177,074 inhabitants in 2019. Located north of the ca ...
in Sweden in 1957. In 1961, a collaboration began between HCL and
Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...
(MGH) to pursue proton therapy. Over the next 41 years, this program refined and expanded these techniques while treating 9,116 patients before the cyclotron was shut down in 2002. In the
USSR The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen nati ...
a therapeutic proton beam with energies up to 200 MeV was obtained at the synchrocyclotron of
JINR The Joint Institute for Nuclear Research (JINR, russian: Объединённый институт ядерных исследований, ОИЯИ), in Dubna, Moscow Oblast (110 km north of Moscow), Russia, is an international research c ...
in
Dubna Dubna ( rus, Дубна́, p=dʊbˈna) is a town in Moscow Oblast, Russia. It has a status of ''naukograd'' (i.e. town of science), being home to the Joint Institute for Nuclear Research, an international nuclear physics research center and one o ...
in 1967. The ITEP center in
Moscow Moscow ( , US chiefly ; rus, links=no, Москва, r=Moskva, p=mɐskˈva, a=Москва.ogg) is the capital and largest city of Russia. The city stands on the Moskva River in Central Russia, with a population estimated at 13.0 million ...
,
Russia Russia (, , ), or the Russian Federation, is a transcontinental country spanning Eastern Europe and Northern Asia. It is the largest country in the world, with its internationally recognised territory covering , and encompassing one-ei ...
, which began treating patients in 1969, is the oldest proton center still in operation. The Paul Scherrer Institute in Switzerland was the world's first proton center to treat eye tumors beginning in 1984. In addition, they invented pencil beam scanning in 1996, which is now the state-of-the art form of proton therapy. The world's first hospital-based proton therapy center was a low energy cyclotron centre for eye tumors at Clatterbridge Centre for Oncology in the UK, opened in 1989, followed in 1990 at the Loma Linda University Medical Center (LLUMC) in Loma Linda, California. Later, the Northeast Proton Therapy Center at
Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...
was brought online, and the HCL treatment program was transferred to it in 2001 and 2002. At the beginning of 2020, there were 37 proton therapy centers in the United States, and a total of 89 worldwide. As of 2020, five manufacturers make proton therapy systems:
Hitachi () is a Japanese multinational conglomerate corporation headquartered in Chiyoda, Tokyo, Japan. It is the parent company of the Hitachi Group (''Hitachi Gurūpu'') and had formed part of the Nissan ''zaibatsu'' and later DKB Group and Fuyo G ...
, Ion Beam Applications, Mevion Medical Systems, ProTom International and Varian Medical Systems.


Types

The newest form of proton therapy, pencil beam scanning, gives therapy by sweeping a proton beam laterally over the target so that it gives the required dose while closely conforming to shape of the targeted tumor. Before the use of pencil beam scanning, oncologists used a scattering method to direct a wide beam toward the tumor.


Passive scattering beam delivery

The first commercially available proton delivery systems used a scattering process, or passive scattering, to deliver the therapy. With scattering proton therapy the proton beam is spread out by scattering devices, and the beam is then shaped by putting items such as collimators and compensators in the path of the protons. Passive scattering gives homogeneous dose along the target volume. Therefore, passive scattering gives more limited control over dose distributions proximal to target. Over time many scattering therapy systems have been upgraded to deliver pencil beam scanning. Because scattering therapy was the first type of proton therapy available, most clinical data available on proton therapy—especially long-term data as of 2020—were acquired via scattering technology.


Pencil beam scanning beam delivery

A newer and more flexible delivery method is pencil beam scanning, using a beam that sweeps laterally over the target so that it delivers the needed dose while closely conforming to the tumor's shape. This conformal delivery is achieved by shaping the dose through magnetic scanning of thin beamlets of protons without needing apertures and compensators. Multiple beams are delivered from different directions, and magnets in the treatment nozzle steer the proton beam to conform to the target volume layer as the dose is painted layer by layer. This type of scanning delivery provides greater flexibility and control, letting the proton dose conform more precisely to the shape of the tumor. Delivery of protons via pencil beam scanning, in use since 1996 at the Paul Scherrer Institute, allows for the most precise type of proton delivery: intensity-modulated proton therapy (IMPT). IMPT is to proton therapy what IMRT is to conventional photon therapy—treatment that more closely conforms to the tumor while avoiding surrounding structures. Virtually all new proton systems now provide pencil beam scanning exclusively. A study led by Memorial Sloan Kettering Cancer Center suggests that IMPT can improve local control when compared to passive scattering for patients with nasal cavity and paranasal sinus malignancies.


Application

It was estimated that by the end of 2019, a total of ~200,000 patients had been treated with proton therapy. Physicians use protons to treat conditions in two broad categories: * Disease sites that respond well to higher doses of radiation, i.e., dose escalation. Dose escalation has sometimes shown a higher probability of "cure" (i.e. local control) than conventional
radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
. These include, among others, uveal
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
(ocular tumor), skull base and paraspinal tumor ( chondrosarcoma and chordoma), and unresectable
sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal ( connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sar ...
. In all these cases proton therapy gives significant improvement in the probability of local control, over conventional radiotherapy. For eye tumors, proton therapy also has high rates of maintaining the natural eye. * Treatment where proton therapy's increased precision reduces unwanted side effects by lessening the dose to normal tissue. In these cases, the tumor dose is the same as in conventional therapy, so there is no expectation of increased probability of curing the disease. Instead, emphasis is on reducing the dose to normal tissue, thus reducing unwanted effects. Two prominent examples are pediatric neoplasms (such as medulloblastoma) and
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...
.


Pediatric

Irreversible long-term side effects of conventional radiation therapy for pediatric cancers are well documented and include growth disorders, neurocognitive toxicity, ototoxicity with subsequent effects on learning and language development, and renal, endocrine and gonadal dysfunctions. Radiation-induced secondary malignancy is another very serious adverse effect that has been reported. As there is minimal exit dose when using proton radiation therapy, dose to surrounding normal tissues can be significantly limited, reducing the acute toxicity which positively impacts the risk for these long-term side effects. Cancers requiring craniospinal irradiation, for example, benefit from the absence of exit dose with proton therapy: dose to the heart, mediastinum, bowel, bladder and other tissues anterior to the vertebrae is eliminated, hence a reduction of acute thoracic, gastrointestinal and bladder side effects.


Eye tumor

Proton therapy for eye tumors is a special case since this treatment requires only relatively low energy protons (~70 MeV). Owing to this low energy, some particle therapy centers only treat eye tumors. Proton, or more generally,
hadron In particle physics, a hadron (; grc, ἁδρός, hadrós; "stout, thick") is a composite subatomic particle made of two or more quarks held together by the strong interaction. They are analogous to molecules that are held together by the ...
therapy of tissue close to the eye affords sophisticated methods to assess the alignment of the eye that can vary significantly from other patient position verification approaches in image guided particle therapy. Position verification and correction must ensure that the radiation spares sensitive tissue like the optic nerve to preserve the patient's vision. For ocular tumors, selecting the type of radiotherapy depends on tumor location and extent, tumor radioresistance (calculating the dose needed to eliminate the tumor), and the therapy's potential toxic side effects on nearby critical structures. For example, proton therapy is an option for retinoblastoma and intraocular melanoma. The advantage of a proton beam is that it has the potential to effectively treat the tumor while sparing sensitive structures of the eye. Given its effectiveness, proton therapy has been described as the "gold standard" treatment for ocular melanoma.


Base of skull cancer

When receiving radiation for skull base tumors, side effects of the radiation can include pituitary hormone dysfunction and visual field deficit—after radiation for pituitary tumors—as well as cranial neuropathy (nerve damage), radiation-induced osteosarcoma (bone cancer), and osteoradionecrosis, which occurs when radiation causes part of the bone in the jaw or skull base to die. Proton therapy has been very effective for people with base of skull tumors. Unlike conventional photon radiation, protons do not penetrate beyond the tumor. Proton therapy lowers the risk of treatment-related side effects from when healthy tissue gets radiation. Clinical studies have found proton therapy to be effective for skull base tumors.


Head and neck tumor

Proton particles do not deposit exit dose, so proton therapy can spare normal tissues far from the tumor. This is particularly useful for head and neck tumors because of the anatomic constraints found in nearly all cancers in this region. The dosimetric advantage unique to proton therapy translates into toxicity reduction. For recurrent head and neck cancer requiring reirradiation, proton therapy is able to maximize a focused dose of radiation to the tumor while minimizing dose to surrounding tissues, hence a minimal acute toxicity profile, even in patients who got multiple prior courses of radiotherapy.


Left-side breast cancer

When
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
— especially in the left breast — is treated with conventional radiation, the lung and heart, which are near the left breast, are particularly susceptible to photon radiation damage. Such damage can eventually cause lung problems (e.g. lung cancer) or various heart problems. Depending on location of the tumor, damage can also occur to the esophagus, or to the chest wall (which can potentially lead to leukemia). One recent study showed that proton therapy has low toxicity to nearby healthy tissues and similar rates of disease control compared with conventional radiation. Other researchers found that proton pencil beam scanning techniques can reduce both the mean heart dose and the internal mammary node dose to essentially zero. Small studies have found that, compared to conventional photon radiation, proton therapy delivers minimal toxic dose to healthy tissues and specifically decreased dose to the heart and lung. Large-scale trials are underway to examine other potential benefits of proton therapy to treat breast cancer.


Lymphoma

Though chemotherapy is the main treatment for lymphoma, consolidative radiation is often used in Hodgkin lymphoma and aggressive non-Hodgkin lymphoma, while definitive treatment with radiation alone is used in a small fraction of lymphoma patients. Unfortunately, treatment-related toxicities caused by chemotherapy agents and radiation exposure to healthy tissues are major concerns for lymphoma survivors. Advanced radiation therapy technologies such as proton therapy may offer significant and clinically relevant advantages such as sparing important organs at risk and decreasing the risk for late normal tissue damage while still achieving the primary goal of disease control. This is especially important for lymphoma patients who are being treated with curative intent and have long life expectancy following therapy.


Prostate cancer

In
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...
cases, the issue is less clear. Some published studies found a reduction in long term rectal and genito-urinary damage when treating with protons rather than
photons A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are Massless particle, massless ...
(meaning
X-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10  nanometers, corresponding to frequencies in the range 30&nb ...
or
gamma ray A gamma ray, also known as gamma radiation (symbol γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically ...
therapy). Others showed a small difference, limited to cases where the prostate is particularly close to certain anatomical structures. The relatively small improvement found may be the result of inconsistent patient set-up and internal organ movement during treatment, which offsets most of the advantage of increased precision. One source suggests that dose errors around 20% can result from motion errors of just . and another that prostate motion is between . The number of cases of prostate cancer diagnosed each year far exceeds those of the other diseases referred to above, and this has led some, but not all, facilities to devote most of their treatment slots to prostate treatments. For example, two hospital facilities devote ~65% and 50% of their proton treatment capacity to prostate cancer, while a third devotes only 7.1%. Worldwide numbers are hard to compile, but one example says that in 2003 ~26% of proton therapy treatments worldwide were for prostate cancer.


Gastrointestinal malignancy

A growing amount of data shows that proton therapy has great potential to increase therapeutic tolerance for patients with GI malignancy. The possibility of decreasing radiation dose to organs at risk may also help facilitate chemotherapy dose escalation or allow new chemotherapy combinations. Proton therapy will play a decisive role for ongoing intensified combined modality treatments for GI cancers. The following review presents the benefits of proton therapy in treating hepatocellular carcinoma, pancreatic cancer and esophageal cancer.


Hepatocellular carcinoma

Post-treatment liver decompensation, and subsequent liver failure, is a risk with radiotherapy for
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...
, the most common type of primary liver cancer. Research shows that proton therapy gives favorable results related to local tumor control, progression-free survival, and overall survival. Other studies, which examine proton therapy compared with conventional photon therapy, show that proton therapy gives improved survival and/or fewer side effects; hence proton therapy could significantly improve clinical outcomes for some patients with liver cancer.


Reirradiation for recurrent cancer

For patients who get local or regional recurrences after their initial radiation therapy, physicians are limited in their treatment options due to their reluctance to give additional photon radiation therapy to tissues that have already been irradiated. Re-irradiation is a potentially curative treatment option for patients with locally recurrent head and neck cancer. In particular, pencil beam scanning may be ideally suited for reirradiation. Research shows the feasibility of using proton therapy with acceptable side effects, even in patients who have had multiple prior courses of photon radiation.


Comparison with other treatments

A large study on comparative effectiveness of proton therapy was published by teams of the
University of Pennsylvania The University of Pennsylvania (also known as Penn or UPenn) is a Private university, private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest- ...
and Washington University in St. Louis in JAMA Oncology, assessing if proton therapy in the setting of concurrent chemoradiotherapy is associated with fewer 90-day unplanned hospitalizations and overall survival compared with concurrent photon therapy and chemoradiotherapy. The study included 1483 adult patients with nonmetastatic, locally advanced cancer treated with concurrent chemoradiotherapy with curative intent and concluded, "proton chemoradiotherapy was associated with significantly reduced acute adverse events that caused unplanned hospitalizations, with similar disease-free and overall survival". A significant number of randomized controlled trials is currently recruiting, but only a limited number have been completed as of August 2020. A phase III
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
of proton beam therapy versus radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma organized by the National Cancer Center in Korea showed better 2-year local progression-free survival for the proton arm and concluded that proton beam therapy (PBT) is "not inferior to RFA in terms of local progression-free survival and safety, denoting that either RFA or PBT can be applied to recurrent small HCC patients". A phase IIB
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
of proton beam therapy versus IMRT for locally advanced
esophageal cancer Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voi ...
organized by University of Texas MD Anderson Cancer Center concluded that proton beam therapy reduced the risk and severity of adverse events compared with IMRT while maintaining similar
progression free survival Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is p ...
. Another Phase II
Randomized Controlled Trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
comparing photons versus protons for
Glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ...
concluded that patients at risk of severe
lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which ...
could benefit from proton therapy. A team from
Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is conside ...
assessed the risk of secondary cancer after primary cancer treatment with external beam radiation using data from the National Cancer Database for 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system. The study included a total of 450,373 patients and concluded that proton therapy was associated with a lower risk of second cancer. The issue of when, whether, and how best to apply this technology is still under discussion by physicians and researchers. One recently introduced method, 'model-based selection', uses comparative treatment plans for IMRT and IMPT in combination with normal tissue complication probability (NTCP) models to identify patients who may benefit most from proton therapy. Clinical trials are underway to examine the comparative efficacy of proton therapy (vs photon radiation) for the following: * Pediatric cancers—by St. Jude Children's Research Hospital, Samsung Medical Center * Base of skull cancer—by Heidelberg University * Head and neck cancer—by MD Anderson, Memorial Sloan Kettering and other centers * Brain and spinal cord cancer—by Massachusetts General Hospital, Uppsala University and other centers, NRG Oncology * Hepatocellular carcinoma (liver)—by NRG Oncology, Chang Gung Memorial Hospital, Loma Linda University * Lung cancer—by Radiation Therapy Oncology Group (RTOG), Proton Collaborative Group (PCG), Mayo Clinic * Esophageal cancer—by NRG Oncology, Abramson Cancer Center, University of Pennsylvania * Breast cancer—by University of Pennsylvania, Proton Collaborative Group (PCG) * Pancreatic cancer—by University of Maryland, Proton Collaborative Group (PCG)


X-ray radiotherapy

The figure at the right of the page shows how beams of X-rays ( IMRT; left frame) and beams of protons (right frame), of different energies, penetrate human tissue. A tumor with a sizable thickness is covered by the IMRT spread out Bragg peak (SOBP) shown as the red lined distribution in the figure. The SOBP is an overlap of several pristine Bragg peaks (blue lines) at staggered depths. Megavoltage X-ray therapy has less "skin scarring potential" than proton therapy: X-ray radiation at the skin, and at very small depths, is lower than for proton therapy. One study estimates that passively scattered proton fields have a slightly higher entrance dose at the skin (~75%) compared to therapeutic megavoltage (MeV) photon beams (~60%). X-ray radiation dose falls off gradually, needlessly harming tissue deeper in the body and damaging the skin and surface tissue opposite the beam entrance. The differences between the two methods depends on: * Width of the SOBP * Depth of the tumor * Number of beams that treat the tumor The X-ray advantage of less harm to skin at the entrance is partially counteracted by harm to skin at exit point. Since X-ray treatments are usually done with multiple exposures from opposite sides, each section of skin is exposed to both entering and exiting X-rays. In proton therapy, skin exposure at the entrance point is higher, but tissues on the opposite side of the body to the tumor get no radiation. Thus, X-ray therapy causes slightly less damage to skin and surface tissues, and proton therapy causes less damage to deeper tissues in front of and beyond the target. An important consideration in comparing these treatments is whether the equipment delivers protons via the scattering method (historically, the most common) or a spot scanning method. Spot scanning can adjust the width of the SOBP on a spot-by-spot basis, which reduces the volume of normal (healthy) tissue inside the high dose region. Also, spot scanning allows for intensity modulated proton therapy (IMPT), which determines individual spot intensities using an optimization algorithm that lets the user balance the competing goals of irradiating tumors while sparing normal tissue. Spot scanning availability depends on the machine and the institution. Spot scanning is more commonly known as
pencil-beam scanning Pencil beam scanning is the practice of steering a beam of radiation or charged particles across an object. It is often used in proton therapy, to reduce unnecessary radiation exposure to surrounding non-cancerous cells. Ionizing radiation Ionizi ...
and is available on IBA, Hitachi
Mevion
(known as HYPERSCAN which became US FDA approved in 2017) and Varian.


Surgery

Physicians base the decision to use surgery or proton therapy (or any radiation therapy) on tumor type, stage, and location. Sometimes surgery is superior (such as cutaneous
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
), sometimes radiation is superior (such as skull base chondrosarcoma), and sometimes are comparable (for example,
prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...
). Sometimes, they are used together (e.g., rectal cancer or early stage breast cancer). The benefit of external beam proton radiation is in the dosimetric difference from external beam X-ray radiation and
brachytherapy Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, pro ...
in cases where use of radiation therapy is already indicated, rather than as a direct competition with surgery. In prostate cancer, the most common indication for proton beam therapy, no clinical study directly comparing proton therapy to surgery, brachytherapy, or other treatments has shown any clinical benefit for proton beam therapy. Indeed, the largest study to date showed that IMRT compared with proton therapy was associated with less gastrointestinal morbidity.


Side effects and risks

Proton therapy is a type of external beam radiotherapy, and shares risks and
side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequenc ...
of other forms of radiation therapy. The dose outside of the treatment region can be significantly less for deep-tissue tumors than X-ray therapy, because proton therapy takes full advantage of the Bragg peak. Proton therapy has been in use for over 40 years, and is a mature technology. As with all medical knowledge, understanding of the interaction of radiations with tumor and normal tissue is still imperfect.


Costs

Historically, proton therapy has been expensive. An analysis published in 2003 found that the cost of proton therapy is ~2.4 times that of X-ray therapies. Newer, less expensive, and dozens more proton treatment centers are driving costs down and they offer more accurate three-dimensional targeting. Higher proton dosage over fewer treatments sessions (1/3 fewer or less) is also driving costs down. Thus the cost is expected to reduce as better proton technology becomes more widely available. An analysis published in 2005 determined that the cost of proton therapy is not unrealistic and should not be the reason for denying patients access to the technology. In some clinical situations, proton beam therapy is clearly superior to the alternatives. A study in 2007 expressed concerns about the effectiveness of proton therapy for prostate cancer, but with the advent of new developments in the technology, such as improved scanning techniques and more precise dose delivery ('
pencil beam scanning Pencil beam scanning is the practice of steering a beam of radiation or charged particles across an object. It is often used in proton therapy, to reduce unnecessary radiation exposure to surrounding non-cancerous cells. Ionizing radiation Ionizi ...
'), this situation may change considerably. Amitabh Chandra, a health economist at Harvard University, said, "Proton-beam therapy is like the Death Star of American medical technology... It's a metaphor for all the problems we have in American medicine." Proton therapy is cost-effective for some types of cancer, but not all. In particular, some other treatments offer better overall value for treatment of prostate cancer. As of 2018, the cost of a single-room particle therapy system is US$40 million, with multi-room systems costing up to US$200 million.


Treatment centers

As of August 2020, there are over 89 particle therapy facilities worldwide, with at least 41 others under construction. As of August 2020, there are 34 operational proton therapy centers in the United States. As of the end of 2015 more than 154,203 patients had been treated worldwide. One hindrance to universal use of the proton in cancer treatment is the size and cost of the cyclotron or
synchrotron A synchrotron is a particular type of cyclic particle accelerator, descended from the cyclotron, in which the accelerating particle beam travels around a fixed closed-loop path. The magnetic field which bends the particle beam into its closed ...
equipment necessary. Several industrial teams are working on development of comparatively small accelerator systems to deliver the proton therapy to patients. Among the technologies being investigated are superconducting synchrocyclotrons (also known as FM Cyclotrons), ultra-compact synchrotrons,
dielectric wall accelerator A Dielectric Wall Accelerator (DWA) is a compact linear particle accelerator concept designed and patented in the late 1990s, that works by inducing a travelling electromagnetic wave in a tube which is constructed mostly from a dielectric materia ...
s, and linear particle accelerators.


United States

Proton treatment centers in the United States (in chronological order of first treatment date) include: The Indiana University Health Proton Therapy Center in Bloomington, Indiana opened in 2004 and ceased operations in 2014.


Outside the US


Australia

In July 2020, construction began for "SAHMRI 2", the second building for the South Australian Health and Medical Research Institute. The building will house the Australian Bragg Centre for Proton Therapy & Research, a addition to the largest health and biomedical precinct in the Southern Hemisphere,
Adelaide Adelaide ( ) is the capital city of South Australia, the state's largest city and the fifth-most populous city in Australia. "Adelaide" may refer to either Greater Adelaide (including the Adelaide Hills) or the Adelaide city centre. The dem ...
's BioMed City. The proton therapy unit is being supplied by ProTom International, which will install its Radiance 330 proton therapy system, the same system used at Massachusetts General Hospital. When in full operation, it will have the ability to treat approximately 600-700 patients per year with around half of these expected to be children and young adults. The facility is expected to be completed in late 2023, with its first patients treated in 2025.


India

Apollo Proton Cancer Centre (APCC) in Chennai, Tamil Nadu, a unit under Apollo Hospitals, is a Cancer specialty hospital. APCC is the only cancer hospital in India with Joint Commission International accreditation.


Israel

In January 2020, it was announced that a proton therapy center would be built in Ichilov Hospital, at the
Tel Aviv Sourasky Medical Center Tel Aviv Sourasky Medical Center ( he, המרכז הרפואי תל אביב ע"ש סוראסקי; commonly referred to as Ichilov Hospital) is the main hospital complex serving Tel Aviv, Israel and its metropolitan area and the second-largest hos ...
. The project's construction was fully funded by donations. It will have two treatment rooms.


Spain

In October 2021, the Amancio Ortega Foundation arranged with the Spanish government and several autonomous communities to donate 280 million euros to install ten proton accelerators in the public health system.


United Kingdom

In 2013 the British government announced that £250 million had been budgeted to establish two centers for advanced radiotherapy:
The Christie NHS Foundation Trust The Christie NHS Foundation Trust in Withington, Manchester, manages the Christie Hospital, one of the largest cancer treatment centres of its type in Europe. The Christie became a NHS Foundation Trust in 2007 and is also an international leader ...
(the
Christie Hospital The Christie Hospital in Manchester, England, is one of the largest cancer treatment centres in Europe. It is managed by The Christie NHS Foundation Trust. History The hospital was established by a committee under the chairmanship of Richard Ch ...
) in
Manchester Manchester () is a city in Greater Manchester, England. It had a population of 552,000 in 2021. It is bordered by the Cheshire Plain to the south, the Pennines to the north and east, and the neighbouring city of Salford to the west. The ...
, which opened in 2018; and University College London Hospitals NHS Foundation Trust, which opened in 2021. These offer high-energy proton therapy, and other types of advanced radiotherapy, including
intensity-modulated radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radiat ...
(IMRT)
and or AND may refer to: Logic, grammar, and computing * Conjunction (grammar), connecting two words, phrases, or clauses * Logical conjunction in mathematical logic, notated as "∧", "⋅", "&", or simple juxtaposition * Bitwise AND, a boolea ...
image-guided radiotherapy (IGRT). In 2014, only low-energy proton therapy was available in the UK, at
Clatterbridge Cancer Centre NHS Foundation Trust The Clatterbridge Cancer Centre (colloquially known as The Royal Cancer Hospital) is an NHS Foundation Trust, which specialises in the treatment of cancer. The centre is one of several specialist hospitals located within Merseyside; alongside ...
in
Merseyside Merseyside ( ) is a metropolitan and ceremonial county in North West England, with a population of 1.38 million. It encompasses both banks of the Mersey Estuary and comprises five metropolitan boroughs: Knowsley, St Helens, Sefton, Wir ...
. But
NHS England NHS England, officially the NHS Commissioning Board, is an executive non-departmental public body of the Department of Health and Social Care. It oversees the budget, planning, delivery and day-to-day operation of the commissioning side of the ...
has paid to have suitable cases treated abroad, mostly in the US. Such cases rose from 18 in 2008 to 122 in 2013, 99 of whom were children. The cost to the National Health Service averaged ~£100,000 per case."Ashya King case: What is proton beam therapy?"
BBC news story with NHS England figures, 31 August 2014


See also

* Particle therapy *
Charged particle therapy Particle therapy is a form of external beam radiotherapy using beams of energetic neutrons, protons, or other heavier positive ions for cancer treatment. The most common type of particle therapy as of August 2021 is proton therapy. In contrast ...
*
Hadron In particle physics, a hadron (; grc, ἁδρός, hadrós; "stout, thick") is a composite subatomic particle made of two or more quarks held together by the strong interaction. They are analogous to molecules that are held together by the ...
* Microbeam *
Fast neutron therapy Fast neutron therapy utilizes high energy neutrons typically between 50 and 70 MeV to treat cancer. Most fast neutron therapy beams are produced by reactors, cyclotrons (d+Be) and linear accelerators. Neutron therapy is currently available in ...
*
Boron neutron capture therapy Neutron capture therapy (NCT) is a type of radiotherapy for treating locally invasive malignant tumors such as primary brain tumors, recurrent cancers of the head and neck region, and cutaneous and extracutaneous melanomas. It is a two-step pro ...
*
Linear energy transfer In dosimetry, linear energy transfer (LET) is the amount of energy that an ionizing particle transfers to the material traversed per unit distance. It describes the action of radiation into matter. It is identical to the retarding force acting o ...
* Electromagnetic radiation and health * Dosimetry *
Ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
* List of oncology-related terms


References


Further reading

* * "Use of Protons for Radiotherapy", A.M. Koehler, Proc. of the Symposium on Pion and Proton Radiotherapy, Nat. Accelerator Lab., (1971). * A.M. Koehler, W.M. Preston, "Protons in Radiation Therapy: comparative Dose Distributions for Protons, Photons and Electrons ''Radiology'' 104(1):191–195 (1972). * "Bragg Peak Proton Radiosurgery for Arteriovenous Malformation of the Brain" R.N. Kjelberg, presented at First Int. Seminar on the Use of Proton Beams in Radiation Therapy, Moscow (1977). * Austin-Seymor, M.J. Munzenrider, et al. "Fractionated Proton Radiation Therapy of Cranial and Intracrainial Tumors" ''Am. J. of Clinical Oncology'' 13(4):327–330 (1990). * "Proton Radiotherapy", Hartford, Zietman, et al. in ''Radiotheraputic Management of Carcinoma of the Prostate'', A. D'Amico and G.E. Hanks. London, UK, Arnold Publishers: 61–72 (1999).


External links

* The Intrepi
Proton-Man
educational comic books by Steve Englehart and Michael Jaszewski for pediatric patients * 2019 BBC Horizo
documentary
* 2019 Jove video by the University of Maryland School of Medicine explaining the treatment process
Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies
* 201
The NHS Proton Beam Therapy Programme
* Proton Therapy Collaborative Grou
PTCOG

Alliance for Proton Therapy

CARES Cancer Network

National Association for Proton Therapy
*
American Society for Radiation Oncology ASTRO (the American Society for Radiation Oncology) is a professional association in radiation oncology Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of ...
Model Policy
Proton Beam Therapy


MedlinePlus MedlinePlus is an online information service produced by the United States National Library of Medicine. The service provides curated consumer health information in English and Spanish with select content in additional languages. The site brings ...
Medical Encyclopedia
Proton Therapy

What is Proton Therapy
{{DEFAULTSORT:Proton therapy Medical physics Radiation therapy procedures Proton